Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration
BackgroundAutophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263988/full |
| _version_ | 1797450863619342336 |
|---|---|
| author | Jun Qin Jun Qin Jun Qin Jin Zhang Jian-Jun Wu Xiao Ru Xiao Ru Qiu-Ling Zhong Qiu-Ling Zhong Jin-Min Zhao Jin-Min Zhao Jin-Min Zhao Jin-Min Zhao Ni-Han Lan Ni-Han Lan |
| author_facet | Jun Qin Jun Qin Jun Qin Jin Zhang Jian-Jun Wu Xiao Ru Xiao Ru Qiu-Ling Zhong Qiu-Ling Zhong Jin-Min Zhao Jin-Min Zhao Jin-Min Zhao Jin-Min Zhao Ni-Han Lan Ni-Han Lan |
| author_sort | Jun Qin |
| collection | DOAJ |
| description | BackgroundAutophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA.MethodsGSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein–protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs.ResultsA total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils.ConclusionCDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy. |
| first_indexed | 2024-03-09T14:46:44Z |
| format | Article |
| id | doaj.art-b6bdc0930fbb40d1add517e41b21539c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T14:46:44Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b6bdc0930fbb40d1add517e41b21539c2023-11-27T06:08:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12639881263988Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltrationJun Qin0Jun Qin1Jun Qin2Jin Zhang3Jian-Jun Wu4Xiao Ru5Xiao Ru6Qiu-Ling Zhong7Qiu-Ling Zhong8Jin-Min Zhao9Jin-Min Zhao10Jin-Min Zhao11Jin-Min Zhao12Ni-Han Lan13Ni-Han Lan14Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Medical Research Center for Orthopedic Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Medical Cosmetology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Orthopedics, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, ChinaGuangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Medical Research Center for Orthopedic Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Medical Research Center for Orthopedic Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Medical Research Center for Orthopedic Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaResearch Centre for Regenerative Medicine, Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Medical Research Center for Orthopedic Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaBackgroundAutophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA.MethodsGSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein–protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs.ResultsA total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils.ConclusionCDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263988/fullosteoarthritiscartilageautophagyimmune cell infiltrationbioinformatics analysis |
| spellingShingle | Jun Qin Jun Qin Jun Qin Jin Zhang Jian-Jun Wu Xiao Ru Xiao Ru Qiu-Ling Zhong Qiu-Ling Zhong Jin-Min Zhao Jin-Min Zhao Jin-Min Zhao Jin-Min Zhao Ni-Han Lan Ni-Han Lan Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration Frontiers in Immunology osteoarthritis cartilage autophagy immune cell infiltration bioinformatics analysis |
| title | Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration |
| title_full | Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration |
| title_fullStr | Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration |
| title_full_unstemmed | Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration |
| title_short | Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration |
| title_sort | identification of autophagy related genes in osteoarthritis articular cartilage and their roles in immune infiltration |
| topic | osteoarthritis cartilage autophagy immune cell infiltration bioinformatics analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263988/full |
| work_keys_str_mv | AT junqin identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT junqin identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT junqin identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT jinzhang identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT jianjunwu identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT xiaoru identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT xiaoru identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT qiulingzhong identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT qiulingzhong identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT jinminzhao identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT jinminzhao identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT jinminzhao identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT jinminzhao identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT nihanlan identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration AT nihanlan identificationofautophagyrelatedgenesinosteoarthritisarticularcartilageandtheirrolesinimmuneinfiltration |